Abstract: α-thalassemia is caused by defects in the α-globin genes (HBA1 and HBA2). The severity of the phe‐ notype is directly related to the number of deleted functional α-globin genes and is also influenced by the types of HBA mutations. Allogeneic hematopoietic stem cell transplantation remains the only curative treatment for transfusion-dependent α -thalassemia, but it is constrained by limited donor availability and the risk of graf-versus-host disease. Gene therapy based on autologous hematopoietic stem cells offers a promising alternative treatment strategy for α -thalassemia. Gene addition therapy aims to restore the number of functional α -globin gene copies by delivering the HBA2 gene via lentiviral vectors. Two related clinical trials (NCT05851105 and NCT05757245) are currently underway in China. Gene editing therapy targeting high-frequency pathogenic non‐ deletional mutations can enhance wild-type α -globin expression and reduce the production of aberrant globin chains. The cytosine base editor (CBE)-based RM-004 therapy achieved transfusion independence in its first clini‐ cal trial participant after treatment. Ongoing refinement and evaluation of gene therapy strategies are expected to offer new curative opportunities for patients with transfusion-dependent α-thalassemia.